The clinical effectiveness of corticoids is related to four basic properties: vasoconstriction, antiproliferative effects, immunosuppression, and anti-inflammatory effects. Topical steroids cause the capillaries in the superficial dermis to constrict, thus reducing erythema. The ability of a given glucocorticoid agent to cause vasoconstriction usually correlates with its anti-inflammatory potency. Vasoconstrictor assays are used in the art and by the U.S. Food and Drug Administration for determining the potency of topical corticosteroid preparations. Topical glucocorticoid preparations have been divided in the field into seven classes based on potency based on double-blind clinical studies and vasoconstrictor assays. Class 1 includes the most potent, while class 7 contains the least potent.
The following glucocorticoid preparations were designated in Fitzpatrick, Dermatology in General Medicine, 5th edition, CD-ROM, 1999, Table 243-1, with the following classes.
TABLE 1CorticosteroidPreparationCorticosteroidClassSourceTemovate ®Clobetasone1Glaxo WellcomeCream 0.05%propionateTemovate ®Clobetasone1Glaxo Wellcomeointment 0.05%propionateDiprolene ®Betamethasone1Schering Corp.cream 0.05%dipropionateDiprolene ®Betamethasone1Schering Corp.ointment 0.05%dipropionatePsorcon ®Diflorasone1Dermik Laboratories,ointmentdiacetateInc.Cyclocort ®Amcinonide2Fujisawaointment 0.1%Diprolene ®Betamethasone2Schering Corp.cream AFdipropionate0.05%Diprosone ®Betamethasone2Schering Corp.ointment 0.05%dipropionateElocon ®Mometasone2Schering Corp.ointment 0.1%furoateFlorone ®Diflorasone2Dermikointment 0.05%diacetateHalog ® creamHalcinonide2Westwood-Squibb0.1%Lidex ® gelFluocinonide2Medicis Pharmaceuticals0.05%Corp.Lidex ® creamFluocinonide2Medicis Pharmaceuticals0.05%Corp.Lidex ®Fluocinonide2Medicis Pharmaceuticalsointment 0.05%Corp.Maxiflor ®Diflorasone2Allergan Herbertointment 0.05%diacetateTopicort ®Desoximetasone2Medicis Pharmaceuticalscream 0.25%Corp.Topicort ® gelDesoximetasone2Medicis Pharmaceuticals0.05%Corp.Topicort ®Desoximetasone2Medicis Pharmaceuticalsointment 0.25%Corp.Aristocort A ®Triamcinolone3Fujisawaointment 0.1%acetonideCutivate ®Fluticasone3Glaxo Wellcomeointmentpropionate0.005%Cyclocort ®Amcinonide3Fujisawacream 0.1%Cyclocort ®Amcinonide3FujisawaLotion 0.1%Diprosone ®Betamethasone3Schering Corp.cream 0.05%dipropionateFlorone ® creamDiflorasone3Dermik0.05%diacetateHalog ®Halcinonide3Westwood-Squibbointment 0.1%Lidex ® EFluocinonide3Medicis Pharmaceuticalcream 0.05%Corp.Maxiflor ®Diflorasone3Allergan Herbertcream 0.05%diacetateValisone ®Betamethasone3Schering Corp.ointment 0.1%valerateCordran ®Flurandrenolide4Oclassenointment 0.05%Elocon ® creamMometasone4Schering Corp.0.1%furoateKenalog ®Triameinolone4Westwood-Squibbcream 0.1%acetonideSynalar ®Fluocinolone4Medicis PharmaceuticalsointmentacetonideCorp.0.025%Westcort ®Hydrocortisone4Westwood-Squibbointment 0.2%valerateCordran ®Flurandrenolide5Oclassencream 0.05%Cutivate ®Fluticasone5Glaxo Wellcomecream 0.05%propionateDiprosone ®Betamethasone5Schering Corp.lotion 0.05%dipropionateKenalog ®Triamcinolone5Westwood-Squibblotion 0.1%acetonideLocoid ® creamHydrocortisone5Ferndale0.1%butyrateSynalar ® creamFlucinolone5Medicis Pharmaceuticals0.025%acetonideCorp.Valisone ®Betamethasone5Schering Corp.cream 0.1%valerateWestcort ®Hydrocortisone5Westwood-Squibbcream 0.2%valerateAclovate ®Alclometasone6Glaxo Wellcomecream 0.05%dipropionateAclovate ®Alclometasone6Glaxo Wellcomeointment 0.05%dipropionateAristocort ®Triamcinolone6Fujisawacream 0.1%acetonideDesowen ®Desonide6Galdermacream 0.05%Synalar ®Fluocinolone6Medicis Pharmaceuticalssolution 0.01%acetonideCorp.Synalar ® creamFluocinolone6Medicis Pharmaceuticals0.01%acetonideCorp.Tridesilon ®Desonide6Milescream 0.05%Valisone ®Betamethasone6Schering Corp.lotion 0.1%valerateTopicals with7hydrocortisonedexamethasone,flumethasone,prednisolone,andmethylprednisolone
All percentages given are weight percentages unless otherwise noted.
Although there is no significant difference between potencies within Class 2, within Class 1 Temovate® cream or ointment is significantly more potent than Class 1 Diprolone® cream or ointment of Schering and Class 1 Psorcon® ointment of Dermik Laboratories, Inc.
Several factors such as the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings affect the percutaneous absorption and resulting potency of corticosteroids regardless of the intrinsic potency of the glucocorticosteroid (or glucocorticoid) molecule. Further, inflammation and/or other disease processes in the skin increase percutaneous absorption.
The vehicle in which the corticoid is incorporated may be as important as the corticoid molecule itself in determining the potency of a given formulation because the vehicle affects the amount of corticoid that is released in any given period of time, and its absorption. In many corticosteroid compositions, the vehicle is as much as 99% of the total composition. Very occlusive vehicles, such as ointments (water-insoluble mixtures of oil and petrolatum), increase the corticosteroid effect because they provide increased hydration of the stratum corneum and increase the skin's permeability. By covering the skin with an occlusive dressing such as plastic wrap, this effect can be heightened as much as 100-fold. The solubility of the corticoid in the vehicle also affects penetration into the skin.
Creams, which are suspensions of oil in water, have also been used as vehicles for corticosteroids. The compositions of creams vary and are far less greasy than ointments but do not provide the same degree of hydration to the skin, and therefore may not have as high penetration as ointments. Lotions, which are suspensions of oil in water and are similar to creams, are vehicles which include agents to help solubilize the corticosteroids. Solutions have been used as vehicles and are water based with propylene glycol. Gels are solid components at room temperature but melt on the skin. Lotions, gels and solutions have less penetration than ointments.
Many vehicles for corticosteroids include propylene glycol for dissolving the corticosteroid in the vehicle. In general, compositions that contain higher amounts of propylene glycol tend to be more potent.
Vehicles are so important in the potency of corticosteroids that different formulations containing the same amount of the same corticosteroid often are in different potency classes. For example, commercially available preparations of 0.05% betamethasone dipropionate are classified as having Class 1, Class 2 or Class 3 potency, depending on their vehicles (as seen in Table 1).